Conserved expression of the GPR151 receptor in habenular axonal projections of vertebrates

The habenula is a phylogenetically conserved brain structure in the epithalamus. It is a major node in the information flow between fronto‐limbic brain regions and monoaminergic brainstem nuclei, and is thus anatomically and functionally ideally positioned to regulate emotional, motivational, and cognitive behaviors. Consequently, the habenula may be critically important in the pathophysiology of psychiatric disorders such as addiction and depression. Here we investigated the expression pattern of GPR151, a G protein–coupled receptor (GPCR), whose mRNA has been identified as highly and specifically enriched in habenular neurons by in situ hybridization and translating ribosome affinity purification (TRAP). In the present immunohistochemical study we demonstrate a pronounced and highly specific expression of the GPR151 protein in the medial and lateral habenula of rodent brain. Specific expression was also seen in efferent habenular fibers projecting to the interpeduncular nucleus, the rostromedial tegmental area, the rhabdoid nucleus, the mesencephalic raphe nuclei, and the dorsal tegmental nucleus. Using confocal microscopy and quantitative colocalization analysis, we found that GPR151‐expressing axons and terminals overlap with cholinergic, substance P‐ergic, and glutamatergic markers. Virtually identical expression patterns were observed in rat, mouse, and zebrafish brains. Our data demonstrate that GPR151 is highly conserved, specific for a subdivision of the habenular neurocircuitry, and constitutes a promising novel target for psychiatric drug development. J. Comp. Neurol. 523:359–380, 2015. © 2014 Wiley Periodicals, Inc.     

Endovascular Aortic Repair in Nonagenarian Patients

BackgroundThe increasing proportion of elderly patients being treated for abdominal aortic aneurysm (AAA) in the endovascular era is controversial.ObjectivesThis study compared 30-day outcomes of endovascular aortic repair (EVAR) in nonagenarians (NAs) with non-nonagenarians (NNAs).MethodsThis retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program database included EVAR procedures performed from 2011 to 2017. Multivariate logistic regression in the unadjusted cohort, followed by propensity-score matching (PSM), was performed. Primary outcomes were 30-day mortality and 30-day major adverse events.ResultsA total of 12,267 patients were included (365 NAs). Ruptured aneurysms accounted for 6.7% (n = 819): 15.7% (n = 57) in NAs versus 6.5% (n = 762) in NNAs (p < 0.001). Mean aneurysm diameter was 6.5 ± 1.8 cm in NAs versus 5.8 ± 1.7 cm in NNAs (p < 0.001). The unadjusted 30-day mortality was 9.9% in NA versus 2.2% in NNAs (p < 0.001). Multivariate analysis revealed age ≥90 years (odds ratio [OR]: 3.36), male sex (OR: 1.78), functional status (OR: 4.22), pre-operative ventilator dependency (OR: 3.80), bleeding disorders (OR: 1.52), dialysis (OR: 2.56), and ruptured aneurysms (OR: 17.21) as independent predictors of mortality. After PSM, no differences in 30-day mortality (intact AAA [iAAA]: 5.3% NA vs. 3% NNA [p = 0.15]; ruptured AAA [rAAA]: 38% NA vs. 28.6% NNA [p = 0.32]) or 30-day major adverse events (iAAA: 7% NA vs. 4.6% NNA [p = 0.22]; rAAA: 28% NA vs. 36.7% NNA [p = 0.35]) were observed.ConclusionsAge was identified as an independent predictor of 30-day mortality after EVAR on multivariate analysis. However, no differences were found after PSM, suggesting that being ≥90 years of age but with similar comorbidities to younger patients is not associated with a higher short-term mortality after EVAR. Age ≥90 years alone should not exclude patients from EVAR, and tailored indications and carefully balanced risk assessment are advised.     

Prognostic significance of risk group stratification in elderly patients with acute myeloid leukaemia

Prognostic factors were studied in a series of 211 acute myeloid leukaemia (AML) patients over 60 years of age, treated at a single centre. The patients were allocated into three risk groups based on cytogenetics, occurrence of antecedent haematological disorder and leucocyte count. Only 3% had low-risk features, 39% had intermediate- and 58% had adverse-risk features. Complete remission (CR) was achieved in 43% of all patients. In multivariate analyses, the number of cycles needed to achieve CR and the risk group were significantly associated with the duration of CR. Median survival time for the entire cohort of patients was only 107 d. Advanced age, low induction treatment intensity, treatment during earlier years and adverse-risk group were associated with shorter overall survival times. Risk group classification may help selection of elderly patients with a good chance of benefiting from intensive treatment to actually receive such treatment, while sparing others with a low probability of survival benefit from toxic treatment. Low intensity induction treatment reduces the chance of obtaining complete remission, produces inferior survival times and should consequently be avoided when the aim is to obtain complete remission. In elderly AML patients, introducing age and re-evaluation of intermediate and good prognosis patients regarding response to induction treatment may improve the risk group classification.     

Axonal excitability changes and acute symptoms of oxaliplatin treatment: In vivo evidence for slowed sodium channel inactivation

Objective

Neurotoxicity is the most frequent dose-limiting side effect of the anti-cancer agent oxaliplatin, but the mechanisms are not well understood. This study used nerve excitability testing to investigate the pathophysiology of the acute neurotoxicity.

Medical follow-up visits in adults 5-25 years after treatment for childhood acute leukaemia, lymphoma or Wilms' tumour

Aim: One aspect of organizing medical follow-up for adult survivors of childhood cancer is to determine to what extent the former patient experiences a need for health services. In the present paper, we studied how the healthcare needs, both subjectively and objectively, were fulfilled for our former patients. Methods: 335 survivors over 18 y of age, with a follow-up time of more than 5 y after completion of therapy, were sent a questionnaire probing their present use of health services. Results: The response rate was 73%. A majority (60%) of the survivors had no regular follow-up visits, and 42% of these reported that they missed not having one. More than one third were thus far dissatisfied with the follow-up programme. Only 3% of those who had regular follow-ups found them “unnecessary”. Complaints subjectively related to their diseases or treatments were reported by 47%. Out of all responders, 34% did not miss having regular follow-up visits. Neither perceived disease-related complaints nor radiation therapy was a predictor for having a scheduled follow-up visit.

Conclusion: In the absence of a long-term follow-up programme, many survivors were not receiving proper medical healthcare, whether from their perspective or from a professional one.     

Multimodal therapy improves survival in patients with CNS metastasis from uterine cancer: a retrospective analysis and literature review

OBJECTIVE: Brain metastasis from uterine cancer is a rare event. Consequently, the optimal management strategy is not defined. We reviewed our institution's experience with brain metastasis from endometrial cancer along with the extant medical literature to develop management recommendations. METHODS: Twenty patients with CNS metastasis were identified. Information regarding symptoms, treatment, and survival was collected. The Kaplan-Meier method was used to compare survival data. RESULTS: The incidence of CNS metastasis was 0.97%. Median patient age at initial diagnosis of endometrial cancer was 62.0 years and 64.0 years at diagnosis of brain metastasis. Most patients initially presented with advanced FIGO stage: 9 stage IVB, 4 stage IIIC, 4 stage IIIA, 2 stage IB, and 1 stage IA. The median interval from diagnosis of endometrial cancer to diagnosis of brain metastasis was 11.5 months (range 0.6-73.6). Median survival after diagnosis of brain metastasis was 2.0 months (range 0.1-39.2). Improved survival was seen in patients treated with multimodal therapy compared to patients who only received whole brain radiotherapy (WBRT) (p=0.0001) or compared to patients who received no treatment (p=0.009). No difference in survival was seen between patients treated with WBRT versus no therapy. The survival advantage associated with multimodal therapy was also supported by case reports and case series in the literature. CONCLUSIONS: Based upon the data presented along with the medical literature, multimodal therapy appears to improve the survival of patients with CNS metastasis from uterine cancer.     

Regional differences in expression of specific markers for human embryonic stem cells

Characterization of human embryonic stem cell (hESC) lines derived from the inner cell masses of blastocysts generally includes expression analysis of markers such as OCT4, NANOG, SSEA3, SSEA4, TRA-1-60 and TRA-1-81. Expression is usually detected by immunocytochemical staining of entire colonies of hESC, using one colony for each individual marker. Four newly established hESC lines showed the expected expression pattern and were capable of differentiating into the three germ layers in vitro. Neighbouring sections of entire colonies grown for 4, 11, 21 and 28 days respectively were stained with different markers to study the regional distribution and cellular co-expression. TRA-1-60 staining defined the hESC territory at all time points analysed. This territory comprised a characteristic OCT4 and NANOG staining often in overlapping subregions. Staining intensity of nuclei varied from strong OCT4 staining to weak or absent NANOG staining, and vice versa. SSEA4 staining was only observed in small clusters or single cells and not confined to the TRA territory. Co-expression of all markers was only detected in small areas. SSEA1 expression was found exclusively outside the TRA territory. In conclusion, pronounced regional differences in the expression of markers considered specific for undifferentiated hESC may suggest the existence of different cell populations.     

Disease activity level, remission and response in established rheumatoid arthritis: Performance of various criteria sets in an observational cohort, treated with anti-TNF agents

Background  

Most composite indices of disease activity and response criteria in RA have been validated and compared in clinical trials rather than routine care. We therefore wanted to compare the performance of the DAS28, SDAI and CDAI activity indices, their activity states, their response criteria, and also compare with the ACR response criteria in an observational clinical setting.